Cannabinoids, such as tetrahydrocannabinol (THC), have gained considerable attention over the past decade for use in treating various conditions such as chronic pain, muscle spasms, chemotherapy induced nausea and vomiting, anorexia, and post-traumatic stress disorder. See e.g., Pharmacology Biochemistry and Behavior 2010, 95 (4): 573-82, Genetic Resources and Crop Evolution 52: 161-180, 2005, and the United States Food and Drug Administration (FDA) approved listing for synthetic cannabinoids Nabilone and Dronabinol. Evidence also suggests that cannabinoids may increase appetite in HIV/AIDS patients, improve sleep, decrease side effects associated with Tourette syndrome, improve asthma and glaucoma, and treat neurological conditions such as multiple sclerosis and epilepsy. Despite these numerous implications, the full therapeutic potential of cannabinoids, e.g., in medicinal cannabis therapies, has yet to be realized.
THC, or more precisely its major isomer (−)trans-Δ9-THC, is perhaps the single most therapeutically active cannabinoid present in medical marijuana. THC exists in eight isomeric forms, four of which are predominant and include (+)trans-Δ8-THC, (−)trans-Δ8-THC, (+)trans-Δ9-THC, and (−)trans-Δ9-THC. The remaining four cis isomers are essentially non-existent in nature and are highly unstable. One of the problems associated with studying THC has been the lack of efficiency in isolating and separating the predominant isomers. For example, conventional normal phase HPLC methods typically do not achieve baseline resolution and have run times typically greater than 20 min.
This challenging problem is important to solve particularly when regulatory bodies such as the FDA require stereoisomeric quantification of drug substances. In addition, chiral separation of THC constituents is also important in legal matters, e.g., to establish the presence or absence of potentially illegal substances, or to create an enanteomeric profile (fingerprint) of the illegal substance, including enanteomeric excess. The need therefore exists to develop a reliable high-throughput method for optimally separating (+)trans-Δ8-THC, (−)trans-Δ8-THC, (+)trans-Δ9-THC, or (−)trans-Δ9-THC from a sample.